SARS1

seryl-tRNA synthetase 1, the group of Aminoacyl tRNA synthetases, Class II

Basic information

Region (hg38): 1:109213917-109238182

Previous symbols: [ "SARS" ]

Links

ENSG00000031698

∙ NCBI:6301 ∙ OMIM:607529 ∙ HGNC:10537 ∙ Uniprot:P49591 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed

Phenotypes

GenCC

Source: genCC

autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with microcephaly, ataxia, and seizures	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Neurologic	28236339

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SARS1 gene.

not provided (8 variants)
Neurodevelopmental disorder with microcephaly, ataxia, and seizures (5 variants)
Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome (2 variants)
Cerebral arteriovenous malformation (1 variants)
See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SARS1 gene is commonly pathogenic or not.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	3	1	5
missense	2	1	1	1		5
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice variant				1	2	3
non coding					2	2
Total	2	1	2	5	5

Variants in SARS1

This is a list of pathogenic ClinVar variants found in the SARS1 region.

Position	Phenotype	Significance	ClinVar
1-109214118-G-A	See cases	Uncertain significance (Oct 06, 2021)	link
1-109228386-C-T	Inborn genetic diseases	Uncertain significance (Jun 01, 2023)	link
1-109228441-T-C	Neurodevelopmental disorder with microcephaly, ataxia, and seizures	Benign (Nov 07, 2021)	link
1-109229572-G-A		Benign (Dec 31, 2019)	link
1-109230944-G-A	Neurodevelopmental disorder with microcephaly, ataxia, and seizures	Pathogenic (Jul 01, 2022)	link
1-109231677-G-T	Neurodevelopmental disorder with microcephaly, ataxia, and seizures	Likely pathogenic (-)	link
1-109235353-G-T		Likely benign (Dec 31, 2019)	link
1-109235366-C-T	Neurodevelopmental disorder with microcephaly, ataxia, and seizures	Pathogenic (Apr 19, 2023)	link
1-109235412-G-A	Neurodevelopmental disorder with microcephaly, ataxia, and seizures	Uncertain significance (Apr 27, 2019)	link
1-109235430-AGGT-A		Uncertain significance (Jun 21, 2023)	link
1-109235955-T-C	Neurodevelopmental disorder with microcephaly, ataxia, and seizures	Benign (Nov 07, 2021)	link
1-109235978-T-C	Cerebral arteriovenous malformation	Pathogenic (Feb 14, 2018)	link
1-109236048-C-T		Likely benign (Jan 30, 2018)	link
1-109236451-G-A	Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome	Benign/Likely benign (Sep 27, 2021)	link
1-109236459-C-T	Neurodevelopmental disorder with microcephaly, ataxia, and seizures	Pathogenic (Apr 19, 2023)	link
1-109236487-C-T	Neurodevelopmental disorder with microcephaly, ataxia, and seizures	Pathogenic (Jun 22, 2023)	link
1-109236555-G-A		Benign (Mar 29, 2018)	link
1-109237312-G-A		Benign (Dec 31, 2019)	link
1-109237381-T-C	Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome	Benign/Likely benign (Feb 15, 2022)	link
1-109237799-A-C	Inborn genetic diseases	Uncertain significance (Aug 19, 2023)	link
1-109237810-G-A		Likely benign (Dec 31, 2019)	link

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SARS1	protein_coding	protein_coding	ENST00000234677	11	24252

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000749	125744	0	3	125747	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.66	170	299	0.568	0.0000170	3378
Missense in Polyphen		36	114.75	0.31372		1309
Synonymous	1.48	94	114	0.823	0.00000639	973
Loss of Function	4.70	2	29.6	0.0675	0.00000175	321

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser- AMP and then transferred to the acceptor end of tRNA(Ser) (PubMed:22353712, PubMed:24095058, PubMed:9431993, PubMed:26433229, PubMed:28236339). Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec) (PubMed:9431993, PubMed:26433229, PubMed:28236339). In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC (PubMed:24940000). Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA (PubMed:19423848, PubMed:19423847, PubMed:24940000). {ECO:0000269|PubMed:19423847, ECO:0000269|PubMed:19423848, ECO:0000269|PubMed:22353712, ECO:0000269|PubMed:24095058, ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:26433229, ECO:0000269|PubMed:28236339, ECO:0000269|PubMed:9431993}.;
Disease: DISEASE: Neurodevelopmental disorder with microcephaly, ataxia, and seizures (NEDMAS) [MIM:617709]: An autosomal recessive disorder characterized by delayed psychomotor development, intellectual disability, seizures apparent in infancy, impaired speech, and aggressive behavior. Additional features include microcephaly, ataxia, and muscle weakness. {ECO:0000269|PubMed:28236339}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);3-Phosphoglycerate dehydrogenase deficiency;Non Ketotic Hyperglycinemia;Glycine and Serine Metabolism;Dimethylglycine Dehydrogenase Deficiency;Hyperglycinemia, non-ketotic;Dimethylglycine Dehydrogenase Deficiency;Sarcosinemia;Dihydropyrimidine Dehydrogenase Deficiency (DHPD);tRNA Aminoacylation;Translation;Selenocysteine synthesis;Metabolism of proteins;Metabolism of amino acids and derivatives;Glycine Serine metabolism;selenocysteine biosynthesis;Metabolism;tRNA charging;Selenoamino acid metabolism;Cytosolic tRNA aminoacylation (Consensus)

Recessive Scores

pRec: 0.261

Intolerance Scores

loftool: 0.145
rvis_EVS: -0.32
rvis_percentile_EVS: 31.69

Haploinsufficiency Scores

pHI: 0.190
hipred: Y
hipred_score: 0.749
ghis: 0.547

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.999

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Sars
Phenotype

Zebrafish Information Network

Gene name: sars
Affected structure: trunk vasculature
Phenotype tag: abnormal
Phenotype quality: branchiness

Gene ontology

Biological process: negative regulation of transcription by RNA polymerase II;translation;tRNA aminoacylation for protein translation;seryl-tRNA aminoacylation;tRNA processing;selenocysteine metabolic process;negative regulation of angiogenesis;selenocysteinyl-tRNA(Sec) biosynthetic process;negative regulation of vascular endothelial growth factor production
Cellular component: nucleus;cytoplasm;cytosol;extracellular exosome
Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA binding;serine-tRNA ligase activity;protein binding;ATP binding;protein homodimerization activity;selenocysteine-tRNA ligase activity